Synthesis of Bis-pyridinium Oxime Antidotes Using Bis(methylsulfonoxymethyl) Ether for Organophosphate Nerve Agents

Abstract

Organophospate nerve agents are organic esters of phosphorous-based acid derivatives and they are extremely toxic chemicals that were first developed before and during World War II primarily for military use. Five organophosphates are generally regarded as nerve agents. They are commonly known as dimethylphosphoramidocyanidic acid ethyl ester (tabun), methylphosphonofluoridic acid (1methylethyl) ester (sarin), methylphosphonofluoridic acid 1,2,2-trimethylpropyl ester (soman), methylphosphonofluoridic acid cyclohexyl ester (cyclosarin), and methylphosphonothioic acid S-[2-[bis(1-methylethyl)amino] ethyl] Oethyl ester (VX). Nerve agents are compounds that exert their biological effects by inhibition of the enzyme acetylcholinesterase (AChE), found at the receptor sites of tissue innervated by the cholinergic nervous system, which hydrolyzes acetylcholine (ACh) very rapidly. The acute toxicity of organophospate compounds in mammals is generally believed to be due to their irreversible inhibition of AChE. Among these organophospate nerve agents, soman is probably one of the most dangerous organophospate agents since its deleterious effects are especially difficult to counteract. Soman seems to cause centrally mediated seizure activity that can rapidly contribute to profound brain damage.